Interleukin 6 (IL-6) and Its Receptor (IL-6R) in Myeloma/Plasmacytoma

  • S. Suematsu
  • M. Hibi
  • T. Sugita
  • M. Saito
  • M. Murakami
  • T. Matsusaka
  • T. Matsuda
  • T. Hirano
  • T. Taga
  • T. Kishimoto
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 166)

Abstract

Interleukin 6 (IL-6) was originally identified as a B cell differentiation factor (BCDF/BSF2) which induces final maturation of B cells into antibody producing cells (Hirano et al 1986). However, subsequent studies with recombinant molecules revealed that IL-6 has a wide variety of biological functions on various tissues and cells (Kishimoto 1989). As shown in Fig. 1, IL-6 acts not only on B cells but also on hematopoietic progenitors and hepatocytes and is involved in hematopoiesis and acute phase reactions. It also acts on nerve cells, epidermal keratinocytes and kidney mesangium cells. One of the most interesting activities is the induction of the growth of myeloma/plasmacytoma cells. IL-6 is a potent growth factor for myelomas/plasmacytomas and only 0.002 ng/ml of rIL-6 could induce 50% of the maximum proliferation in a human myeloma cell line (Muraguchi et al 1988). This concentration of IL-6 is 100-fold less than that required for the immunoglobulin induction in B cells.

Keywords

Albumin Lymphoma Leukemia Cysteine Polypeptide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aguet M, Dembic Z, Merlin G (1988) Molecular cloning and expression of the human interferon-Yreceptor. Cell 55: 273–280.PubMedCrossRefGoogle Scholar
  2. Bazan JF (1989) A novel family of growth factor receptors: a common binding domain in the growth hormone, prolactin, erythropoietin and IL-6 receptors, and the p75 IL-2 receptor β chain. Biochem Biophys Res Commun 164: 788–795.PubMedCrossRefGoogle Scholar
  3. Canaani E, Dreaxen O, Klar A, Rechavi G, Earn D, Cohen JB, Givol D. (1983) Activation of the c-mos oncogene in a mouse plasmacytoma by insertion of an endogenous intracisternal A-particle genome. Proc Natl Acad Sci USA 80: 7118–722.PubMedCrossRefGoogle Scholar
  4. Gearing DP, King JA, Gough NM, Nicola NA (1989) Expression cloning of a receptor for human granulocyte=macrophage colony-stimulating factor. EMBO J 8: 3667–3676.PubMedGoogle Scholar
  5. Gray PW, Leong S, Fennie EH, Farrar MA, Pingel JT, Fernandez-Luna J, Schreiber RD (1989) Cloning and expression of the cDNA for the murine interferon γ receptor. Proc Natl Acad Sci USA 86: 8497–8501.PubMedCrossRefGoogle Scholar
  6. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatu A, Tsunasawa S, Sakiyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T (186) Complementary cDNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324: 73–76.Google Scholar
  7. Hirata Y, Taga T, Hibi M, Nakano N, Hirano T, Kishimoto T (1989) Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies. J Immunol 143: 2900–2906.PubMedGoogle Scholar
  8. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T (1988) Automne generation and essential requirements of BSF-2/IL-6 for human multiple myeloma. Nature 332: 83–85.PubMedCrossRefGoogle Scholar
  9. Kishimoto T (1989) The biology of interleukin 6. Blood 74: 1–10.PubMedGoogle Scholar
  10. Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T (1988) The essential role of B cell stimulatory factor 2 (BSF-2/TL-6) for the terminal differentiation of B cells. J Exp Med 167: 332–344.PubMedCrossRefGoogle Scholar
  11. Ohno S, Babonits M, Wiener F, Spira J, Klein G, Potter M (1979) Non-random chromosome changes involving the Ig-gene carrying chromosomes 12 and 6 in pristane-induced mouse plasmacytomas. Cell 18: 1001–1007.PubMedCrossRefGoogle Scholar
  12. Potter M, Boyce C (1962) Induction of plasma-cell neoplasms in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature 193: 1086–1087.PubMedCrossRefGoogle Scholar
  13. Schrader JW, Crapper RM (1983) Autogenous production of ahemopoietic growth factor, persisting-cell-stimulating factor, as a mechanism for transformation of bone marrow-derived cells. Proc Natl Acad Sci USA 80: 6892–6896.PubMedCrossRefGoogle Scholar
  14. Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM, Friend D, Alpert AR, Gillis S, Urdal DL, Dower SK (1988) cDNA expression cloning fo the IL-1 receptor, a member of the immunoglobulin superfamily. Science 241: 585–589.PubMedCrossRefGoogle Scholar
  15. Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S, Miyazaki J, Yamamura K, Hirano T, Kishimoto T (1989) IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 86: 7547–7551.PubMedCrossRefGoogle Scholar
  16. Sugita T, Totsuka T, Saito M, Yamasaki K, Taga T, Hirano T, Kishimoto T (to be published) Functional murine interleukin 6 receptor with the intracisternal a particle gene product at its cytoplasmic domain. J Exp MedGoogle Scholar
  17. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirata T, Kishimoto T (1989) Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58: 573–581.PubMedCrossRefGoogle Scholar
  18. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFNβ) receptor. Science 241: 825–828.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • S. Suematsu
    • 1
  • M. Hibi
    • 1
  • T. Sugita
    • 1
  • M. Saito
    • 1
  • M. Murakami
    • 1
  • T. Matsusaka
    • 1
  • T. Matsuda
    • 1
  • T. Hirano
    • 1
  • T. Taga
    • 1
  • T. Kishimoto
    • 1
  1. 1.Institute for Molecular and Cellular BiologyOsaka UniversityOsakaJapan

Personalised recommendations